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bioRxiv · 10.1101/2020.02.19.956946

Structural basis for the recognition of the 2019-nCoV by human ACE2

Yan, R.·Zhang, Y.·Guo, Y.·Xia, L.·Zhou, Q.
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Abstract

Angiotensin-converting enzyme 2 (ACE2) has been suggested to be the cellular receptor for the new coronavirus (2019-nCoV) that is causing the coronavirus disease 2019 (COVID-19). Like other coronaviruses such as the SARS-CoV, the 2019-nCoV uses the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) to engage ACE2. We most recently determined the structure of the full-length human ACE2 in complex with a neutral amino acid transporter B0AT1. Here we report the cryo-EM structure of the full-length human ACE2 bound to the RBD of the 2019-nCoV at an overall resolution of 2.9 [A] in the presence of B0AT1. The local resolution at the ACE2-RBD interface is 3.5 [A], allowing analysis of the detailed interactions between the RBD and the receptor. Similar to that for the SARS-CoV, the RBD of the 2019-nCoV is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. Pairwise comparison reveals a number of variations that may determine the different affinities between ACE2 and the RBDs from these two related viruses.

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Yan, R., Zhang, Y., Guo, Y., Xia, L., Zhou, Q.. 2020-02-20. Structural basis for the recognition of the 2019-nCoV by human ACE2. https://doi.org/10.1101/2020.02.19.956946

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